DELAYED MACROPHAGE RESPONSES AND MYELIN CLEARANCE DURING WALLERIAN DEGENERATION IN THE CENTRAL-NERVOUS-SYSTEM - THE DORSAL RADICULOTOMY MODEL
DELAYED MACROPHAGE RESPONSES AND MYELIN CLEARANCE DURING WALLERIAN DEGENERATION IN THE CENTRAL-NERVOUS-SYSTEM - THE DORSAL RADICULOTOMY MODEL
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DOI：
10.1006/exnr.1994.1164
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发表时间：
1994-10-01
影响因子：
5.3
通讯作者：
GRIFFIN, JW
中科院分区：
文献类型：
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作者：
GEORGE, R;GRIFFIN, JW
沃勒变性（Wallerian degeneration，WD）的各个方面——轴突崩解、神经胶质细胞和巨噬细胞的反应以及髓鞘碎片的清除——通常被认为在中枢神经系统（CNS）中发生得比在周围神经系统（PNS）中更慢。我们通过比较神经纤维中穿过PNS和CNS的节段的沃勒变性的时间模式来重新评估这个问题。大鼠的L(4)、L(5)和L(6)背根被横断，使用电子显微镜和免疫染色来识别和表征不同细胞类型，在长达8个月的时间间隔内对背根和背柱中的沃勒变性进行比较。这些轴突的轴浆在PNS和CNS部分在72小时内都完成了初始崩解。与PNS相比，WD的所有其他方面在CNS中都显著延迟。巨噬细胞（来自循环系统）在根中的数量增加（轴突切断后2 - 4天）。相比之下，尽管在退变的背柱中有一个早期且短暂的小胶质细胞激活期（在第3天达到峰值），但圆形巨噬细胞的出现延迟到第18 - 21天。在PNS中，轴突碎片和髓鞘碎片在30天内几乎完全被清除，但在CNS中则保留超过90天。轴突再生在背根中很活跃，但这些芽突没有侵入背柱。背根进入区在PNS和CNS的沃勒变性模式之间提供了明显的解剖分界。这些结果表明，循环中的巨噬细胞容易进入退变的周围神经，但在很大程度上或完全被排除在退变的CNS束之外，因此（最终出现的）巨噬细胞主要来源于星形小胶质细胞。(C) 1994学术出版社
All aspects of Wallerian degeneration (WD)-axonal breakdown, glial and macrophage responses, and clearance of myelin debris-have generally been considered to occur more slowly in the central nervous system (CNS) than in the peripheral nervous system (PNS). We reevaluated this issue by comparing the temporal pattern of Wallerian degeneration in nerve fibers with segments extending through both the PNS and the CNS. The L(4), L(5), and L(6) dorsal roots in the rat were transected, and WD in the dorsal roots and the dorsal columns was compared at intervals up to 8 months, using electron microscopy and immunostaining to identify and characterize the different cell types. The initial breakdown of axoplasm was complete by 72 h both in the PNS and in the CNS portions of these axons. All other aspects of WD were strikingly delayed in the CNS when compared to those in the PNS. Macrophages (from the circulation) increased in number (Days 2-4 after axotomy) in the root. In contrast, although there was an early and transient period (peaking at Day 3) of microglial activation in the degenerating dorsal column, the appearance of round macrophages was delayed until Days 18-21. Both axonal debris and myelin debris were almost completely cleared by 30 days in the PNS, but remained over 90 days in the CNS. Axonal regeneration was vigorous in the dorsal root but these sprouts did not invade the dorsal columns. The dorsal root entry zone provided a sharp anatomic demarcation between the PNS and CNS patterns of Wallerian degeneration. These results suggest that circulating macrophages have ready access to degenerating peripheral nerves, but are largely or completely excluded from degenerating CNS tracts, so that the macrophages (that ultimately appear) originate primarily from the stellate microglia. (C) 1994 Academic Press, Inc.